Osteoarthritis (degenerative joint disease) is the most common form of arthritis. Therapy at present is symptomatic rather than specific. Although the etiology of osteoarthritis is unknown, recent studies have allowed formulation of new concepts of pathogenesis. The overall objectives of this proposal are: 1) to advance the understanding of normal cartilage metabolism and cartilage pathophysiology, particularly as it applies to the osteoarthritic process, and 2) to develop therapeutic agents which will interrupt the pathologic process. Specific studies being carried out include evaluation from different joint regions and at different ages; analysis and study of metabolic changes taking place in developing osteoarthritis; the effects of estrogen and related sex hormones on normal cartilage metabolism and the osteoarthritic process; isolation, purification and identification of the nature of neutral proteinases and collagenases/inhibitors derived from chondrocytes in culture; delineation of component changes in proteoglycan interrelationships of chondrocyte prostaglandins and prostaglandins and hydrolytic enzymes.